A wide variety of bacterial species produce acylated homoserine lactone (AHL) derivatives that function in cell-cell communication. This signaling system is used, for example, to monitor population cell density in a process called quorum sensing. Each cell in a population produces a low basal level of the diffusible AHL via the activity of an AHL synthase, usually a member of the LuxI family of proteins. The AHL concentration increases with bacterial population density until the AHL concentration is sufficient to cause expression of various AHL-dependent genes via an AHL receptor protein, usually a member of the LuxR family of transcription regulators. In at least some species, the AHL synthase gene is inducible by AHL, leading to auto-induction of AHL synthesis. Quorum sensing systems have been described in Vibrio fischeri (lux bioluminescence genes), Pseudomonas aeruginosa (virulence genes), Agrobacterium tumefaciens (conjugal transfer), Serratia liquefaciens (swarming motility), and Erwinia caratovora (antibiotic production), for example. For reviews, see, e.g.: Fuqua and Greenberg, Curr. Opinion Microbiol. 1:183-189, 1998; and Fuqua et al., Ann. Rev. Microbiol. 50:727-751, 1996).
According to published studies of the LuxR-LuxI quorum sensing system of Vibrio fischeri, specific binding to the LuxR binding site (or “lux box”) within the lux promoter sequences was not observed with either LuxR alone or bacterial RNA polymerase alone, but required the presence of both LuxR and RNA polymerase. Thus, it has been thought that inducible gene expression under the control of LuxR is possible only when bacterial RNA polymerase is also present, i.e., in bacterial cells, limiting the utility of quorum sensing systems in eukaryotic cells.
A number of systems have been described for regulating eukaryotic gene, including various promoter elements that are chemically inducible. However, there remains a need for an inducible promoter system that can be used in a variety of eukaryotic organisms, that is strictly regulated and strongly induced, and that responds to a chemical inducer that has low cytotoxicity.